Canadian integrated program for antimicrobial resistance surveillance (CIPARS): Key and integrated findings

Year 2024 2023

Ceftriaxone-resistance in non-typhoidal Salmonella, S. Heidelberg, and E. coli from chicken(s) and/or people, and third generation cephalosporin use/sales.

Importance:

Third generation cephalosporins are considered of very high importance to human medicine^{Footnote 1} in Canada and around the world^{Footnote 2}. While salmonellosis is often not treated in people, if treatment is needed, third generation cephalosporins are one of the only treatment options for children and pregnant women^{Footnote 3}. Heidelberg is a serovar of Salmonella (i.e., a strain of Salmonella) that tends to make people very sick^{Footnote 3Footnote 4}.

Data to action:

Historically, in Canada, Salmonella Heidelberg was one of the most commonly reported third-generation cephalosporin-resistant Salmonella serovars recovered from poultry and people^{Footnote 5}. A third-generation cephalosporin (ceftiofur) was used in chickens to prevent E. coli omphalitis^{Footnote 5}.

Following a voluntary withdrawal of ceftiofur for use in disease prevention by the poultry industry in 2005 and then again in 2014, there was a reduction in the frequency of ceftriaxone resistance in Salmonella from broiler chickens (both healthy chickens on farm and at abattoir (i.e., at slaughter), sick chickens (clinical cases)) and in chicken purchased at the grocery store (Figure 1). Importantly, there was also a reduction in ceftriaxone-resistant S. Heidelberg in people (Figure 1).

In chicken(s), this trend was also observed in E. coli (Figure 1) adding further evidence to a common selective pressure for the resistant determinant. Ceftriaxone-resistant S. Heidelberg has not been found in healthy broiler chicken on farm since 2018. From 2003 to 2019, S. Heidelberg was a top 3 serovar from humans composing 6 to 21% of human Salmonella isolates. However, in 2023 in humans, S. Heidelberg contributed to less than 1% of isolates and was not in the top 10 serovars.

2024 data updates

The conclusions of the story remain the same. The recovery of Salmonella Heidelberg continues to decrease across host species. Ceftriaxone resistance in S. Heidelberg continues to exist at low-levels in humans (4.8% in 2024) and there remains no ceftriaxone resistance in S. Heidelberg from broiler chickens (both healthy chickens on farm and at abattoir), diagnostic clinical submissions from chickens, or in retail chicken. The frequency of ceftriaxone resistance remained low (<6%) in E. coli isolates from samples from broiler chickens (both healthy chickens on farm and at abattoir) and retail chicken.

Ceftiofur was not reported to be used in hatcheries supplying broiler chicken farms participating in CIPARS sentinel farm surveillance. Whereas, ceftriaxone use in humans has continued to rise in both the hospital (hospital purchases) and community settings (dispensations from community pharmacies)^{Footnote i}.

Figure 1. CIPARS-FNC: Frequency of ceftriaxone resistance in non-typhoidal Salmonella and Escherichia coli isolates from chicken(s) and/or people, and ceftiofur use in broiler chicken flocks.

Hover over the line or bar graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).

Increasing frequency of ESBL-producing non-typhoidal Salmonella from humans, animals and food

Importance:

Extended-spectrum β-lactamase (ESBL)-producing Salmonella are resistant to third-generation cephalosporins. Salmonella are part of the Enterobacterales order. ESBL-producing Enterobacterales are in the ‘Tier 1: High-priority’ group of antimicrobial-resistant pathogens of concern in Canada^{Footnote 1} and a critical group according to the World Health Organization’s Bacterial Priority Pathogens List, 2024^{Footnote 2}.

What the data are telling us:

ESBL-producing non-typhoidal Salmonella (NTS) from humans and animal/food sources continues to steadily increase (Figure 1). Of all the Salmonella tested, the frequency of ESBL-producing Salmonella in 2017 was 0.5% for humans (n = 27 ESBL isolates/5010 total NTS isolates) and 0.3% for animals and food (n = 6/2372). Whereas in 2023, the frequencies rose to 1.6% (n = 91/5843) and 1.6% (n = 36/2208), respectively (Figure 1).

In humans, of all ESBLs, the predominant ESBL gene (bla_CTX-M-65) decreased from 66% in 2019 to 42% in 2023 and the majority were found in S. Infantis (n = 33). Whereas the second most predominant ESBL gene, bla_CTX-M-55, increased from 13% in 2019 to 37% in 2023. The majority of these bla_CTX-M-55 carrying isolates were Salmonella I 4,[5],12:i:- (n = 22).

In animals/food, of all ESBL carrying isolates, the predominant ESBL gene was bla_CTX-M-65, which increased from 24% in 2018, to 59% in 2022 to 80% in 2023. In 2023, the majority of these bla_CTX-M-65 carrying isolates were S. Infantis (n = 21).

2024 data updates

ESBL-producing NTS isolates recovered from humans and animals/food continued to increase, with a sharp increase in animals/food between 2023 and 2024. Of all the NTS tested, the frequency of ESBL-producing NTS was 1.9% and 2.7% from humans and animals/food, respectively in 2024. CTX-M-65 increased in both animal/food sources and humans. Salmonella Infantis was the most common serovar with this gene, 95% and 92% of CTX-M-65 from humans and animals/food, respectively from 2017 and 2024. In humans, the frequency of CTX-M-55 increased since 2017, while in animals/food, the frequency of this gene of all NTS tested was variable ranging from 0.1% to 0.4% across years. Salmonella I 4,[5],12:i:- was the most common serovar with this gene, 60% and 37% of CTX-M-55 from humans and animals/food, respectively from 2017 and 2024.

Figure 1. CIPARS-FNC: Frequency of ESBL-producing non-typhoidal Salmonella from humans, animals and food.

Hover over the line or bar graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph.

Nalidixic acid resistance in Salmonella Enteritidis from chicken(s)

Importance:

Salmonella Enteritidis isolates from chickens and chicken meat were historically almost 100% susceptible to all the antimicrobials that CIPARS tested. However, in 2018 CIPARS reported the emergence of nalidixic acid-resistant S. Enteritidis from chicken(s). Nalidixic acid is a quinolone and resistance to quinolones can often be a precursor to resistance to fluoroquinolones. These isolates with nalidixic acid resistance also had reduced susceptibility to fluoroquinolones. Fluoroquinolones are considered of very high importance to human medicine^{Footnote 1} in Canada and around the world^{Footnote 2}.

Salmonella Enteritidis is one of the top serovars that we find in people with salmonellosis and one of the top serovars we see in chicken(s).

What the data are telling us:

In 2018, nalidixic acid resistance in S. Enteritidis was first detected in CIPARS isolates (n = 5 isolates) from healthy chickens at slaughter, sick chickens (clinical cases) and chicken meat (Figure 1). These proportions were mostly stable until 2022 when CIPARS observed a substantial spike in resistance across farm, abattoir, retail, and diagnostic chicken isolates (Figure 1). In 2023, nalidixic acid resistance was found in the following components/sources: chicken meat (n = 21 resistant isolates/70 total S. Enteritidis isolates), diagnostic samples from sick chickens (n = 31/78), healthy chicken at slaughter (n = 6/31) and healthy broiler chickens on farm (n = 10/29) (Figure 1).

This spike in resistance appears to be driven by a GyrA (D87Y) substitution. Further genomic analyses are on-going, including looking at the genes in the human S. Enteritidis isolates.

2024 data updates

Nalidixic acid resistance in S. Enteritidis continues to increase in isolates from healthy chickens at abattoir and retail chicken. There were also substantial increases in nalidixic acid resistance in human S. Enteritidis isolates, with resistance approaching a frequency of 60% in 2024.

Since 2018, all nalidixic acid-resistant S. Enteritidis isolates from broiler chickens (farm, abattoir and clinical cases) and retail, were sequence type 11 and had a mutation (D87Y) in the gyrA gene. The mutation in the gyrase A gene results in an amino acid change (D87Y) in the gyrase A protein (which is the target of fluoroquinolones). In humans, S. Enteritidis isolates with this mutation in gyrA (D87Y) substantially increased as well, with 99.4% of these isolates also being of sequence type 11.

Complicating the situation, in humans, we are also seeing this mutation in S. Infantis, rising from 11% of Infantis isolates in 2017 to 42% in 2024.

Figure 1. CIPARS-FNC: Frequency of nalidixic acid resistance in Salmonella Enteritidis from chicken(s)

Hover over the line graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).

Ciprofloxacin resistance in Campylobacter and fluoroquinolones sold for use in animals and people.

Importance:

CIPARS has been watching an increasing trend in ciprofloxacin resistance in Campylobacter across multiple animal species and at different stages along the food chain. Ciprofloxacin is a fluoroquinolone. Fluoroquinolones are considered of very high importance to human medicine^{Footnote 1} in Canada and around the world^{Footnote 2}.

What the data are telling us:

Between 2022 and 2023, an increase in ciprofloxacin resistance was observed in Campylobacter recovered from all terrestrial food animal species under surveillance at the farm-level (broiler chickens, layer chickensd^{Footnote i}, turkeys, pigs, dairy cattle and feedlot cattle). Across the food animal species (farm-level), the magnitude of the increase (percentage difference) during this time frame was between 2% and 20%, with high frequencies of ciprofloxacin resistance in 2023 ranging between 19% and 46%. Further genomic analyses are on-going to understand this trend across multiple host species.

The human Campylobacter data are from clinical cases reported within FoodNet Canada. Overall, ciprofloxacin resistance in Campylobacter from humans has remained stable, based on data available up to 2022. In C. jejuni, resistance levels were high in 2018 and 2022 (32% and 30%, respectively), although there was a decreasing trend between 2019 (45%) to 2022 (30%). In C. colid^{Footnote ii}, ciprofloxacin resistance was 70% in 2018 and 60% in 2022, but there was an increasing trend between 2020 (33%) and 2022 (60%).

In 2023, more fluoroquinolones were sold (or intended for use) in humansd^{Footnote iii} than animals (human range: 4.16 to 5.60 mg/kg biomass vs. animal range: 0.04 to 0.11 mg/kg biomass). Between 2019 and 2023, the quantity of fluoroquinolones intended for use in humans decreased by 26% (5.60 to 4.16 mg/kg biomass). Whereas in animals, the quantity of fluoroquinolones sold by manufacturers and importers, while small relative to other antimicrobial classes, increased by 38% (0.08 to 0.11 mg/kg biomassd^{Footnote iv}).

2024 data updates

Ciprofloxacin resistance in Campylobacter from feedlot cattle, dairy cattle, and healthy cattle at abattoir continued to rise. The increase in feedlot cattle was significant and substantial between 2023 and 2024, with the frequency of resistance approaching 60% in 2024.

The story seems to be changing in the other species at different stages of the food chain, where fluoroquinolone resistance in Campylobacter is becoming more variable or even decreasing in broiler chickens on farm^{Footnote v} and in retail turkey. For humans, the trend has been variable with high frequencies of resistance ranging between 25-44% across the years and resistance of 35% in 2024.

In 2024, more fluoroquinolones were sold (or intended for use) in humans^{Footnote iii} than animals^{Footnote 3} (humans: 3.97 mg/population-adjusted biomass vs. animals: 0.16 mg/kg biomass). Between 2020 and 2024, the quantity of fluoroquinolones intended for use in humans decreased by 14% (4.63 to 3.97 mg/population-adjusted biomass).

In animals, the quantity of fluoroquinolones sold by manufacturers and importers, while small relative to other antimicrobial classes, increased by 220% (0.05 to 0.16 mg/kg biomass)^{Footnote iv}.

Figure 1. CIPARS-FNC: Frequency of ciprofloxacin-resistance in Campylobacter from humans, animals and food

Hover over the line graph to see more details. Click on a legend element to add or remove the corresponding lines from the graph. Red text in the hover over field highlights a small total isolate count (less than 20).